P501: ISATUXIMAB PLUS CHEMOTHERAPY FOR PEDIATRIC RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA OR ACUTE MYELOID LEUKEMIA (ISAKIDS): INTERIM EFFICACY ANALYSIS
Authors: André Baruchel, Yves Bertrand, Karsten Nysom, Hyoung Jin Kang, Monica Makiya, Jonas Abrahamsson, Oscar González-Llano, Willy Quinones Choque, Carmelo Rizzari, Jochen Buechner, Simone Cesaro, Ximo Duarte, Franca Fagioli, Antonis Kattamis, Guy Leverger, Brigitte Nelken, Lynn Wang, Sandrine Mace, Corina Oprea, Giovanni Abbadessa, Michel Zwaan
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Elevated CD38 expression is present in acute pediatric leukemias, making CD38 a potential target for treating children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Isatuximab (ISA), a monoclonal antibody that binds to a specific epitope of CD38, is approved for use in relapsed-refractory (R/R) multiple myeloma in adults. ISAKIDS (NCT03860844) is a planned 2-stage study investigating ISA in combination with standard salvage chemotherapies (CT) in children with R/R ALL or AML in first or second relapse. Aims: To define the efficacy (complete response [CR] rate) and toxicity of ISA in combination with CT in R/R pediatric ALL or AML. Methods: This Phase 2, single-arm, multicenter, open-label study enrolled children aged 28 days (d) to <18 years (yrs). Patients (pts) in 3 separate cohorts (T-ALL, B-ALL, AML) received induction therapy with ISA 20 mg/kg on d1 and then weekly for a total of 5 weeks (ALL groups) or 3 weeks (AML group). CT was added on d8. Participants with signs of response to induction therapy could proceed to consolidation therapy with every-2-week ISA x 2 doses plus CT (T-ALL, B-ALL) or an optional second similar induction cycle (AML). The primary endpoint was CR rate, defined as the proportion of pts with CR or CR with incomplete peripheral blood count recovery (CRi) in the evaluable population. Pts were considered evaluable for response if they received ≥1 complete ISA administration in the initial induction therapy cycle and had ≥1 valid response assessment. The number of evaluable pts required to draw significant conclusions from this interim analysis was 11 (T-ALL) and 23 (B-ALL, AML). Prespecified CR rate thresholds to proceed to Stage 2 of the study were ≥60% (T-ALL) and ≥70% (B-ALL and AML). Secondary endpoints included minimal residual disease (MRD) status and overall response rate. Safety analyses included treatment-emergent adverse events (TEAEs) of all grades. Results: Here, we present results of the prespecified interim efficacy analysis, conducted after full Stage 1 enrollment. Baseline characteristics among 67 enrolled and treated pts (27 B-ALL, 13 T-ALL, 27 AML) included respective median age (range) of 7 (3–16), 9 (1.4–16), and 10 (2–17) yrs, and percentage male of 63.0%, 69.2%, and 55.6%. Most pts in the B-ALL cohort were in second relapse; most in the T-ALL and AML cohorts were in first relapse. Among 61 pts assessed locally for CD38 expression, all except 2 (1 B-ALL and 1 AML) were CD38-positive. 59 of 67 treated pts were evaluable for response per protocol; CR/CRi was observed for 13/25 (52.0%) in the B-ALL cohort, 5/11 (45.5%) in the T-ALL cohort, and 14/23 (60.9%) in the AML cohort (Figure). MRD and survival data analyses will be presented later. The most common all-grade TEAEs (by preferred term) were pyrexia, infusion-related reaction, and febrile neutropenia (43.3% each). Infusion reactions (majority Grade 1 or 2) occurred in 29/67 pts (9/27 B-ALL; 5/13 T-ALL; 15/27 AML). Grade ≥3 TEAEs occurred in 53/67 pts. Seven pts had Grade 5 TEAEs (4 B-ALL, 3 AML); only one (cytokine release syndrome in an AML pt, with high white blood cell count [188 x 109/L] as a risk factor and progressive disease as a confounding factor) was deemed ISA-related. Summary/Conclusion: No unexpected safety issues were observed when ISA was added to standard CT. In a poor-prognostic R/R population of pediatric leukemia pts, 32/59 (54.2%) evaluable pts achieved CR or CRi. Despite some initial evidence of efficacy, CR/CRi rates in individual cohorts did not meet prespecified criteria to proceed to Stage 2 of the ISAKIDS trial.Keywords: Relapse, Pediatric, Leukemia